This program project grant brings together physiologists, biochemists, chemists and clinicians to investigate fundamental aspects of the physiology, biochemistry and pharamacology of the gonadotropin releasing peptide, LRF. The aim of this program is the elucidation of: the mode of biosynthesis of LRF by the analysis of putative precursor molecules; the distribution and characteristics of LRF receptors in pituitary, gonads and nervous system; the modulation mechanism of cellular responses to LRF by prior exposure to LRF and folliculostatin; the chemical and biological characterization of folliculostatin; the definition of the structural requirements of receptor recognition and transduction by means of novel conformationally restricted analogs of LRF agonists and antagonists; the physiologic roles of LRF in human and animal reproductive processes as probed by means of highly potent competitive LRF antagonists; the mechanisms of anti-reproductive actions of high doses of LRF or potent LRF agonists in vivo; and the potential significance of potent LRF agonists and antagonists as regulators of fertility.